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Biomedical subjects

M M Kaplan

Publications and source records attributed to M M Kaplan.

At least 55 records · Page 3Linked to original sources
PubMed1995

Synthesis of interleukin-1 beta in primary biliary cirrhosis: relationship to treatment with methotrexate or colchicine and disease progression.

Primary biliary cirrhosis (PBC) is a chronic, progressive, cholestatic liver disease. Interleukin-1 beta (IL-1 beta) may play a role in the pathogenesis of PBC by contributing to altered immune function and fibrosis. Colchicine or methotrexate has some beneficial effects in the treatment of PBC, and also affects interleukin-1 (IL-1). Therefore, we prospectively studied the synthesis of IL-1 beta by peripheral blood mononuclear cells (PBMC) from 42 patients with PBC entered into a randomized, double-blind, double-dummy controlled trial of colchicine and methotrexate. PBMC obtained at entry, 6, 12, 18, and 24 months were stimulated to produce IL-1 beta with phytohemagglutinin (PHA), lipopolysaccharide (LPS), Staphylococcus epidermidis, recombinant IL-2, or mitochondrial antigen. Patients in the two treatment groups did not differ at entry in biochemical measures or liver histological stage. Over 24 months in both groups, serum bilirubin and histologic stage remained stable and alkaline phosphatase decreased significantly. For all patients, synthesis of IL-1 beta increased constitutively and in response to immune-mediated stimulants (PHA, IL-2, and mitochondrial antigen) but not the bacterial stimulants LPS or S epidermidis. Compared with levels of IL-1 beta at entry, PHA induced increases for patients treated with methotrexate (12, 18, and 24 months) or colchicine (18 and 24 months). At 24 months, IL-2-induced IL-1 beta synthesis was increased in patients treated with methotrexate, whereas S epidermidis-induced IL-1 beta was enhanced in colchicine-treated patients. Before treatment, IL-1 beta production did not relate to severity of disease except in response to S epidermidis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Hepatic copper content is normal in early primary biliary cirrhosis and primary sclerosing cholangitis.

In previous studies, the majority of patients with the cholestatic liver diseases, primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC), had increased hepatic copper (Cu) levels even in early stages of disease. We prospectively measured hepatic copper content by atomic absorption spectrophotometry in 55 patients with PBC, 6 patients with PSC, and 29 patients with other chronic noncholestatic liver diseases. Hepatic Cu content was normal in 22/61 (36%) of patients with PBC or PSC; 18 of the 22 did not have cirrhosis (82%). Hepatic Cu content increased with increasing stage of disease (r = 0.61, P < 0.001) and was positively correlated with serum total bilirubin (r = 0.6, P < 0.0001) and alkaline phosphatase (r = 0.5, P < 0.001). All patients with stage I and II disease had hepatic Cu < 150 micrograms/g dry weight, and all patients with hepatic Cu > 150 micrograms/g dry weight had stage III and IV disease. Hepatic Cu content is normal in early PBC and PSC. Copper accumulation in the liver in these cholestatic liver diseases is secondary to cholestasis rather than a primary phenomenon.

Alkaline Phosphatase↗
PubMed1994

Interstitial pneumonitis after low-dose methotrexate therapy in primary biliary cirrhosis.

Interstitial pneumonitis is an uncommon complication of low-dose methotrexate therapy in patients with psoriasis but occurs in 3%-5% of patients with rheumatoid arthritis. We found a higher incidence of interstitial pneumonitis in patients with primary biliary cirrhosis (14%) and describe its clinical manifestations, treatment, and possible etiology. Blood tests, arterial blood gas determinations, chest radiographs, bronchoscopy, tear production, autoantibody tests, and serum immunoglobulin levels were obtained in six women who developed interstitial pneumonitis while receiving methotrexate in a double-blind prospective trial of methotrexate vs. colchicine in 87 patients with primary biliary cirrhosis. Six of 43 patients (14%) who received methotrexate compared with no patients receiving colchicine developed interstitial pneumonitis 19-61 weeks after starting treatment. The pneumonitis was characterized by dyspnea, hypoxemia, and bilateral lung infiltrates, all of which responded within 24 hours to the administration of intravenous glucocorticoids. There was no correlation between the pneumonitis and pre-existing lung disease, the severity of the primary biliary cirrhosis, the titer of antimitochondrial antibody, or other diseases associated with primary biliary cirrhosis. Patients with primary biliary cirrhosis receiving low-dose methotrexate (15 mg/wk) are more susceptible to interstitial pneumonitis than patients with psoriasis or rheumatoid arthritis. The pneumonitis appears to be a hypersensitivity reaction and responds rapidly to intravenous glucocorticoid therapy.

Aged↗
PubMed1994

A double-blind controlled trial of oral-pulse methotrexate therapy in the treatment of primary sclerosing cholangitis.

BACKGROUND/AIMS: Primary sclerosing cholangitis (PSC) is a progressive disease with no accepted effective treatment. Because methotrexate was associated with clinical and histological improvement in two men with PSC, we conducted a prospective trial of methotrexate in PSC. METHODS: A prospective placebo-controlled, double-blind trial of methotrexate in PSC was performed. Twenty-four patients with PSC were randomized to receive methotrexate or placebo for a 2-year period. Seven of 12 taking methotrexate and five taking placebo had cirrhosis. Serial liver biopsies, endoscopic retrograde cholangiopancreatography (ERCP), and biochemical tests of liver function were followed. RESULTS: There were no significant changes in liver histological results, ERCP findings, tests of liver function (other than alkaline phosphatase), or outcome between the two groups. Mean alkaline phosphatase levels decreased by 152 IU in the methotrexate group and increased by 30 IU in the placebo group (P = 0.032). Patients taking methotrexate were more likely to reduce or discontinue cholestyramine than patients taking placebo. CONCLUSIONS: This study does not support efficacy for methotrexate in the treatment of PSC. On the basis of this study, the empiric use of methotrexate in patients with PSC is not recommended. However, methotrexate is being further evaluated in patients with precirrhotic PSC.

Adolescent↗
PubMed1993

Cytomegalovirus immune globulin prophylaxis in liver transplantation. A randomized, double-blind, placebo-controlled trial.

OBJECTIVE: To study the effect of cytomegalovirus immune globulin (CMVIG) on prevention of cytomegalovirus (CMV) disease and its complications in patients receiving liver transplants. DESIGN: Randomized, multicenter, placebo-controlled, double-blind trial. SETTING: Four university-affiliated transplant centers in Boston (Boston Center for Liver Transplantation). PATIENTS: One hundred forty-one liver transplant recipients completed the study. INTERVENTION: CMVIG or placebo (1% albumin) given in a dose of 150 mg/kg body weight within 72 hours of the transplant, then at weeks 2, 4, 6, and 8, and at 100 mg/kg at weeks 12 and 16. MEASUREMENTS: Patients were observed for 1 year after transplantation for the development of CMV infection, disease, pneumonia, as well as for opportunistic fungal infections, graft survival, and mortality. Weekly cultures were taken of urine, buffy coat, and throat wash for CMV for 2 months, then monthly, and at any clinical illness. RESULTS: Using a Cox proportional hazards model, CMVIG was shown to reduce severe CMV-associated disease (multi-organ CMV disease, CMV pneumonia, or invasive fungal disease associated with CMV infection) from 26% to 12% (relative risk, 0.39; 95% CI, 0.17 to 0.89). When we controlled for the use of monoclonal antibodies to T cells (OKT3), CMVIG use was still protective (relative risk, 0.39; CI, 0.17 to 0.90). Rates of CMV disease were reduced from 31% to 19% (relative risk, 0.56; CI, 0.3 to 1.1) in CMVIG recipients although no effect on rates of CMV infection, graft survival, or patient survival at 1 year were shown. When we controlled for the urgency of transplantation and OKT3 use, a reduction in CMV disease (relative risk, 0.22; CI, 0.06 to 0.81) was shown for globulin recipients for all serologic groups except for the highest risk group (the CMV-seropositive donor, CMV-seronegative group). CONCLUSION: CMVIG reduced the rate of severe CMV-associated disease in patients undergoing orthotopic liver transplantation. No effect of CMVIG on CMV donor-positive, recipient-negative liver transplant recipients was shown, suggesting a need for additional prophylactic strategies.

Acyclovir↗
PubMed1993

Antipyrine kinetics in patients with primary biliary cirrhosis.

Fourteen antimitochrodrial antibody-positive patients (13 women, 1 man) with biopsy-proven primary biliary cirrhosis, aged 40 to 71 years (mean, 57 years) weighing 43 to 102 kg (mean, 63 kg), along with 14 age- and sex-matched healthy controls, received a single 1.0- to 1.2-g dose of intravenous antipyrine. Plasma antipyrine levels were determined during a 12- to 24-hour period. Patients' mean serum chemistry values were: albumin, 3.9 g/dL (range, 3.1-4.4) and total bilirubin, 1.9 mg/dL (range, 0.3-10.9). Seven of the fourteen patients had cirrhosis. Mean kinetic variables for antipyrine in controls and primary biliary cirrhosis patients were: Vd, .54 versus .49 L/kg; half-life, 12.0 versus 15.1 hours (P < .07); clearance, .55 versus .41 mL/min/kg (P < .04). Within the primary biliary cirrhosis group, there was no correlation between total bilirubin and clearance (r = .09), nor did clearance vary significantly among histologic categories. Clearance of antipyrine in primary biliary cirrhosis patients is reduced by an average of 25%, but the clinical prognosticators of serum bilirubin levels and histologic grade do not correlate with or predict the degree of clearance impairment.

Adult↗
PubMed1993

Reduced tissue thyroid hormone levels in fatal illness.

Patients with severe nonthyroidal illnesses (NTIs) frequently have decreased serum concentrations of triiodothyronine (T3) and less often of thyroxine (T4) without clear evidence of hypothyroidism. To determine whether T3 and T4 levels are also reduced in the tissues, we analyzed autopsy samples from 12 patients dying of NTI and 10 previously healthy individuals dying suddenly from trauma. Mean serum T3, T4, and free T4 index values were lower by 79%, 71%, and 49%, respectively, in the NTI group than in controls, but serum thyrotropin (TSH) values did not differ significantly. Mean T3 concentrations in cerebral cortex, hypothalamus, pituitary, liver, kidney, and lung were lower in the NTI group than in controls by 43% to 76%, but mean values in heart and skeletal muscle did not differ significantly between the groups. The mean liver T4 concentration was 66% lower in the NTI group, but mean T4 concentrations in the cerebral cortex were similar in the two groups. These results indicate that many tissues may be deficient in thyroid hormones in patients with fatal NTI, although the severity of the reduction in thyroid hormone concentrations may vary from one organ to another.

Adult↗
PubMed1993

Thyroid hormone therapy. What, when, and how much.

Hypothyroidism is the condition most commonly treated with exogenous thyroid hormone. The goal of therapy is to normalize levels of serum thyrotropin (thyroid-stimulating hormone), which should be monitored by a high-sensitivity test. Adjustments in optimal dose may be necessary for a number of physiologic reasons (eg, decreased gastrointestinal absorption, pregnancy). Thyroid hormone therapy is also appropriate after surgery for thyroid cancer and for patients with goiter or benign thyroid nodules. In the absence of hypothyroidism, such treatment should not be used for obesity, fatigue, irregular menses, or infertility.

Humans↗
PubMed1993

Tissue specificity and serologic reactivity of an autoantigen associated with autoimmune thyroid disease.

A recent report has identified a new autoantigen called D1 that appears to be associated with Graves' ophthalmopathy and is expressed in the thyroid and eye muscle. To better characterize the tissue specificity and disease relevance of this antigen, we evaluated the expression of D1 RNA in various human tissues using a reverse transcriptase polymerase chain reaction assay. These studies indicate a wide tissue distribution of the messenger RNA for this antigen, including the thyroid, eye muscle, parathyroid, spleen, skeletal muscle, and uterus. There were variations in the relative amounts of specific message for D1 in the different tissues, with the uterus, thyroid, and eye muscle having the greatest amount of product per microgram of total RNA. A maltose binding protein-D1 fusion protein was expressed in Escherichia coli, purified, and used to assess serologic reactivity to D1 by Western blot. Autoantibodies to this antigen were noted in 19 of 24 (78%) of Hashimoto's disease patients, 26 of 41 (63%) of Graves' disease patients, and in 9 of 17 (53%) of normal controls. Sixty percent of Graves' disease patients with clinical ophthalmopathy had antibodies to D1, as did 63% of Graves' patients without signs or symptoms of clinical ophthalmopathy. There was no correlation between reactivity to D1 and either clinical measures of hyperthyroidism or antibody titers to thyroid peroxidase or thyroglobulin. The presence of autoantibodies to this antigen in patients with Hashimoto's disease, in Graves' disease patients without ophthalmopathy and in normal controls indicate that serologic recognition of this antigen is not restricted to patients with ophthalmopathy. In addition, the expression of messenger RNA for this antigen in multiple types of cells questions the tissue specificity of this autoantigen.

Adult↗
PubMed1993

Differential autoantibody responses to thyroid peroxidase in patients with Graves' disease and Hashimoto's thyroiditis.

In order to examine the specificity of the autoantibody response to thyroid peroxidase (TPO, previously identified as thyroid microsomal antigen) in autoimmune thyroid disease, we examined reactivity of sera from 45 Hashimoto's and 48 Graves' patients to native thyroid microsomes, denatured and reduced human TPO and several recombinant fragments of human TPO corresponding to amino acids 457-933 of the native protein. Both Graves' and Hashimoto's sera bound native, denatured and reduced TPO at significantly greater rate than normal controls, and no differences were noted between the two disorders in binding to these forms of the autoantigen. Binding was also noted to two recombinant fragments of TPO, corresponding to amino acids 513-633 and 633-933 in TPO. The frequency of autoantibodies to the TPO AA(633-933) region was not significantly different in Hashimoto's vs. Graves' disease patients (58% vs. 65% respectively), and appeared to relate to evidence of glandular inflammation in the Graves' patients (presence of anti-thyroglobulin antibodies and elevated anti-microsomal antibody levels). In contrast, antibodies to the TPO AA(513-633) fragment were significantly more common and of higher titer in Hashimoto's vs. Graves' disease patients, and did not correlate with any measure of glandular inflammation. These results identify two specific regions of TPO autoantibody binding and indicate that there are differences in the autoantibody response to TPO in Hashimoto's and Graves' diseases.

Adolescent↗
PubMed1993

Treatment of primary biliary cirrhosis.

Primary biliary cirrhosis (PBC) is a chronic, progressive disorder characterized by destruction of small and medium-sized bile ducts within the liver. Current evidence suggests that liver damage in this condition may occur via immunological and nonimmunological mechanisms. The immunological element is mediated by activated T lymphocytes, which are directed toward biliary epithelial cells. Destruction of biliary epithelium may lead to impaired secretion and subsequently increased concentrations of hydrophobic, toxic bile acids in the microenvironment of the hepatic lobule. These bile acids may in turn damage hepatocyte membranes and may also exacerbate secondary reactive immune-mediated destruction of both bile ducts and hepatic parenchyma. Long-standing inflammation may lead to hepatic fibrosis and, ultimately, cirrhosis. Although a variety of agents have been used to treat PBC with variable efficacy, the most promising treatment regimens appear to be those that combine an immunomodulatory agent, such as methotrexate, with a water-soluble bile salt, such as ursodeoxycholic acid. Colchicine, which may modulate cytokine activity and decrease fibrosis, may also have a role in treatment. Because PBC is a chronic, slowly progressive disease, long-term treatment trials, such as those currently under way, will be needed to assess the real benefit of such regimens. Meanwhile, liver transplantation has an excellent success rate in patients with advanced PBC, and should be used in patients with decompensated liver disease.

Humans↗
PubMed1992

Lymphadenopathy in sclerosing cholangitis: pitfall in the diagnosis of malignant biliary obstruction.

We retrospectively reviewed abdominal computed tomographic (CT) studies from 20 patients with sclerosing cholangitis and found evidence of abdominal lymphadenopathy in 13 patients. Enlargement occurred primarily in areas draining the liver, such as the gastrohepatic ligament or celiac axis (N = 8), the porta hepatis (N = 7), and the pancreaticoduodenal region (N = 2). One patient had reactive adenopathy and retroperitoneal fibrosis. The presence of benign reactive lymphadenopathy in at least one intraabdominal location was confirmed by pathological examination of excised lymph nodes in seven patients. Malignancy was excluded by surgical exploration or clinical follow-up. We conclude that enlarged lymph nodes are a common finding by CT in patients with sclerosing cholangitis. Enlarged reactive lymph nodes in this condition should not be mistaken for evidence of periportal metastasis or cholangiocarcinoma.

Adenoma, Bile Duct↗